Introduction
Promoting healthier and more sustainable food consumption requires a global shift towards more plant-based diets [
1]. Current Western diets, which are high in energy and animal-based foods, contribute heavily to the growing global burden of chronic diseases and environmental degradation. The detrimental effects on health and the environment have been attributed particularly to high red and processed meat consumption [
2‐
6]. Hence, reducing their consumption has been highlighted in different international strategies [
1,
7] and dietary recommendations [
8‐
12]. In contrast, increasing the consumption of plant-based foods, such as whole grains, vegetables, fruits and legumes, has been recommended because of their associations with beneficial health effects [
3,
4,
13‐
15] and low greenhouse gas emissions [
2]. As in other Western countries [
16], in Finland, red and processed meat consumption exceeds recommendations, especially in men, while the consumption of plant-based foods remains insufficient [
17].
Strong evidence indicates that consumption of red meat and processed meat are associated with an increased risk of colorectal cancer (CRC) [
6,
18]. In 2020, CRC was the third most common cancer in the world with 1.9 million new cases diagnosed [
19]. The International Agency for Research on Cancer (IARC) has classified red meat as probably carcinogenic and processed meat as carcinogenic, mainly based on evidence of increased CRC risk [
6]. Similarly, the World Cancer Research Fund (WCRF) recommends limiting red and processed meat consumption as red meat is considered a probable and processed meat a convincing cause of CRC [
18]. In the meta-analyses conducted by the WCRF and the American Institute for Cancer Research (AICR), a 100 g/d increase in red meat consumption was associated with a 12% higher CRC risk and a 50 g/d increase in processed meat consumption with an 18% higher risk [
13]. In contrast, the WCRF/AICR reported a 17% decrease in CRC risk for each 90 g/d increase in whole grain intake. A small 2% risk reduction also occurred with a 100 g/d increase in vegetable consumption. The WCRF/AICR meta-analyses included 6 − 11 cohort studies with 6000 − 14 000 CRC cases [
13].
While the need for reducing red and processed meat consumption and eating more plant-based diets is evident, the implications of substituting red and processed meat with plant-based foods on CRC risk are ill-defined. Based on the displayed associations between single food groups and CRC risk, substituting red and processed meats with plant-based foods would presumably decrease CRC risk [
13]. The total impact of a dietary shift on disease risk may not, however, directly reflect the summed impacts of single food groups. Moreover, the associations may vary depending on which plant-based foods are substituted for animal-based foods.
To date, few studies have assessed CRC risk in relation to dietary shifts towards more plant-based diets, and the focus has been on shifting sources of protein intake. A large cohort study including 490 000 US Americans and 9000 incident CRC cases modelled substitutions of total protein intake from red meat with plant-based protein and reported 11% lower CRC risk in the highest substitution quintile compared with the lowest quintile [
20]. In an Italian cohort study (
n = 45 000, 538 incident CRC cases), substituting 3% of energy intake from red and processed meat-derived protein with plant-based protein was associated with a decreased rectal cancer risk [
21]. The substitution was also associated with an increased colon cancer risk, but this association was driven by plant-based proteins from foods with high glycaemic index.
The previous studies have not examined substitutions of red meat and processed meat separately in relation to CRC, even though processed meat seems to be a stronger risk factor for CRC than red meat is [
6]. Similarly, no study has explored substitutions of red meat or processed meat with whole grains, vegetables, fruits or legumes in relation to CRC risk. Consequently, we aimed to examine partial substitutions of red meat (100 g/week) or processed meat (50 g/week) with corresponding amounts of whole grains, vegetables, fruits, legumes or a combination of these in relation to CRC risk in Finnish adults. We modelled moderate substitutions of 100 g or 50 g per week to explore dietary changes that would be easy to implement and maintain in real-life settings.
Results
We present results from analyses of women and men combined because of a small number of CRC cases in women and because no interaction occurred between the sexes. Among the 43 788 participants, the median follow-up was 28.8 years (range 7.8 − 29.9 years), during which 1124 CRCs were diagnosed (Table
1). The median age at baseline ranged from 50 (Health 2000) to 60 years (HBCS) (Table
2). ATBC differed from the other cohorts by having a higher proportion of participants with low educational attainment (78% vs. 30 − 34%) and smokers (100% vs. 17 − 26%). The proportion of participants physically inactive in leisure time ranged from 19% (DILGOM 2007) to 42% (ATBC). Regarding dietary intake, participants in ATBC tended to consume more dairy products, alcohol, processed meat and whole grains, and fewer vegetables, fruits and legumes than participants in the other cohorts. For example, average processed meat consumption in ATBC was double that in HBCS (420 vs. 210 g/week), while vegetable consumption in ATBC was less than half the amount consumed in the other cohorts (658 vs. 1526 − 1848 g/week). Legume consumption was low in all cohorts (28 − 70 g/week).
Table 2
Baseline characteristics of the participants included in the pooled analyses by cohorts (medians and interquartile ranges [IQR] or percentages)
Age, years | 57 (8) | 50 (22) | 60 (4) | 53 (22) | 53 (24) |
Low educational attainmenta, % | 78 | 33 | 34 | 30 | 33 |
Current smoker, % | 100 | 26 | 24 | 18 | 17 |
Inactive in leisure time, % | 42 | 28 | 31 | 19 | 20 |
Body mass index, kg/m2 | 26 (5) | 26 (6) | 27 (6) | 26 (6) | 26 (6) |
HRT use (women), ever % | - | 31 | 68 | 16 | 14 |
Energy, MJ/d | 10.8 (4.0) | 9.1 (3.9) | 8.7 (4.0) | 9.9 (4.5) | 8.9 (4.1) |
Dietary fibre, g/d | 17 (13) | 23 (13) | 25 (14) | 29 (16) | 24 (14) |
Alcohol (100%), g/d | 11 (23) | 2 (7) | 5 (11) | 4 (9) | 4 (9) |
Dairy products, g/d | 699 (502) | 546 (466) | 436 (435) | 584 (509) | 579 (516) |
Substitution variables | | | | | |
Red meat, g/week | 455 (273) | 511 (343) | 420 (350) | 511 (406) | 462 (357) |
Processed meat, g/week | 420 (406) | 252 (336) | 210 (280) | 280 (350) | 266 (343) |
Whole grainsb, g/week | 700 (595) | 406 (406) | 378 (357) | 532 (441) | 483 (455) |
Vegetablesc, g/week | 658 (588) | 1526 (1295) | 1722 (1449) | 1848 (1533) | 1589 (1323) |
Fruits, g/week | 756 (819) | 1099 (1435) | 1512 (1897) | 1491 (1687) | 1085 (1274) |
Legumes, g/week | 28 (35) | 63 (63) | 56 (63) | 70 (70) | 70 (70) |
Red meat consumption was associated with a 76% higher and processed meat consumption with a 26% higher CRC risk among participants in the highest consumption quintile (Q5) compared with those in the lowest quintile (Q1) (red meat: HR 1.76, 95% CI 1.05 − 2.94,
P-trend = 0.041; processed meat: 1.26, 1.00 − 1.59,
P = 0.026; model 2) (Online Resource
4). With the amounts used in the substitution analyses, both red meat (100 g/week; 1.03, 1.00 − 1.06,
P = 0.027; model 2) and processed meat were associated with small increases in CRC risk, although for processed meat, the association was statistically significant only in model 1 (50 g/week; 1.01, 1.00 − 1.02,
P = 0.027). We also observed a direct association between legume consumption and CRC risk (100 g/week; 1.14, 1.05 − 1.25,
P = 0.003; model 2). Conversely, fruit consumption had an inverse association with CRC risk (100 g/week; 0.99, 0.98 − 1.00,
P = 0.049; model 2). Otherwise, we observed no associations between the plant-based foods and CRC risk.
In the substitution analyses, we observed small decreases in CRC risk when 100 g/week of red meat was substituted with a corresponding amount of vegetables (0.97, 0.95 − 0.99,
P = 0.008; model 2), fruits (0.97, 0.94 − 0.99,
P = 0.007; model 2) or a combination of whole grains, vegetables and fruits (0.97, 0.95 − 0.99,
P = 0.012; model 2) (Table
3). Similarly, we detected small risk reductions when processed meat (50 g/week) was substituted with vegetables (0.99, 0.98 − 1.00,
P = 0.029, model 2) or fruits (0.99, 0.98 − 1.00,
P = 0.036; model 2). Substituting red meat with whole grains and processed meat with the plant-based foods combined were also associated with a decreased CRC risk, but statistically significantly only in model 1. No notable heterogeneity occurred between the cohorts. Excluding participants who consumed red meat < 100 g/week or processed meat < 50 g/week attenuated the associations between the processed meat substitutions and CRC risk (
Pvegetables=0.06,
Pfruits=0.08; model 2). The results remained the same after we excluded participants diagnosed with CRC within the first two years of follow-up and, in ATBC, after we adjusted the analyses for family history of CRC (data not shown).
Table 3
Pooled associations between partial substitutions of red meat or processed meat with whole grains, vegetables, fruits, or a combination of these and colorectal cancer risk (hazard ratios [HR] and 95% confidence intervals [CI])
Substitution of red meat (100 g/week) with | | | | | |
Whole grainsd, 100 g/week | 0.94 (0.89, 1.00) | 0.047 | 0.96 (0.91, 1.01) | 0.12 | 0.22 |
Vegetablese, 100 g/week | 0.97 (0.94, 0.99) | 0.004 | 0.97 (0.95, 0.99) | 0.008 | 0.67 |
Fruits, 100 g/week | 0.96 (0.93, 0.99) | 0.002 | 0.97 (0.94, 0.99) | 0.007 | 0.48 |
Whole grains, vegetables and fruits, 100 g/week | 0.96 (0.94, 0.99) | 0.004 | 0.97 (0.95, 0.99) | 0.012 | 0.44 |
Substitution of processed meat (50 g/week) with | | | | | |
Whole grainsd, 50 g/week | 0.98 (0.96, 1.01) | 0.11 | 0.99 (0.98, 1.00) | 0.25 | 0.73 |
Vegetablese, 50 g/week | 0.99 (0.98, 1.00) | 0.033 | 0.99 (0.98, 1.00) | 0.029 | 0.81 |
Fruits, 50 g/week | 0.99 (0.98, 1.00) | 0.016 | 0.99 (0.98, 1.00) | 0.036 | 0.80 |
Whole grains, vegetables and fruits, 50 g/week | 0.99 (0.98, 1.00) | 0.035 | 0.99 (0.98, 1.00) | 0.07 | 0.88 |
After excluding ATBC from the cohorts, we observed a statistically significant 7% decrease in CRC risk when red meat was substituted with whole grains (0.93, 0.87 − 0.99,
P = 0.021; model 2). Excluding ATBC also slightly strengthened the inverse associations between CRC risk and substituting red meat with vegetables (0.96, 0.93 − 1.00,
P = 0.028; model 2), fruits (0.95, 0.92 − 0.98,
P = 0.002; model 2) or the plant-based foods combined (0.97, 0.93 − 0.99,
P = 0.004; model 2) (Online Resource
5). The associations between the processed meat substitutions and CRC risk remained essentially the same, although the 1% risk reductions following the substitutions with vegetables or fruits were no longer statistically significant.
Doubling the substitutions to 200 g/week for red meat and 100 g/week for processed meat resulted in somewhat larger risk reductions. Substituting red meat with vegetables, fruits, or the plant-based foods combined reduced CRC risk by 6%, 7% and 6%, respectively (vegetables: 0.94, 0.89 − 0.98, P = 0.008; fruits: 0.93, 0.89 − 0.98, P = 0.007; the plant-based foods combined: 0.94, 0.89 − 0.99, P = 0.012; model 2). For processed meat, the substitutions with vegetables or fruits resulted in borderline 2% risk reductions. After increasing the processed meat substitution to 200 g/week, these risk reductions increased to 4% (vegetables: 0.96, 0.92 − 1.00, P = 0.029; fruits: 0.96, 0.93 − 1.00, P = 0.036; model 2).
We observed no interactions between the substitutions (red meat: 100 g/week; processed meat: 50 g/week) and sex, age, BMI, HRT use, or follow-up time (data not shown). When the substitutions with whole grains were examined separately for those with < median or ≥ median whole grain intake, we detected significant interactions for both red meat and processed meat (pinteraction=0.001). Among participants with < median whole grain intake, substituting red meat or processed meat with whole grains was associated with 8% and 4% decreases in CRC risk, respectively (red meat: 0.92, 0.86 − 0.98; processed meat: 0.96, 0.93 − 0.99; model 2), while no statistically significant associations occurred among those with ≥ median whole grain intake (red meat: 0.99, 0.94 − 1.05; processed meat: 1.00, 0.99 − 1.01; model 2).
Discussion
In this pooled analysis of five large Finnish cohorts, substitutions of 100 g/week of red meat or 50 g/week of processed meat with a corresponding amount of vegetables or fruits were associated with small decreases in CRC risk. We observed no association between substitutions of red or processed meat with whole grains and CRC risk in the total population. However, among participants with < median whole grain intake, substitutions with whole grains resulted in up to 8% reduction in CRC risk.
Substitutions of red meat or processed meat with whole grains, vegetables or fruits have not been examined previously in relation to CRC risk. In a study exploring
protein substitutions within a large US cohort (
n = 490 000), no association was observed between replacing protein from red meat with protein from vegetables and fruits and CRC risk [
20]. Similarly, in an Italian study (
n = 45 000), no association was observed between replacing 3% of energy intake from animal protein with plant-based protein from low glycaemic index foods (pasta, vegetables, fruits and legumes) and the risk of colon or rectal cancer.
In this study, the associations observed between the substitutions and CRC risk were modest. We had expected to detect stronger associations, particularly regarding processed meat substitutions, given the compelling evidence in the literature on the carcinogenicity of processed meat consumption [
6]. Overall, the modest results are likely attributed to the nonsignificant or small associations between the food groups individually and CRC risk; consumption of processed meat (50 g/week), whole grains (100 g/week) and vegetables (100 g/week) had no statistically significant association with CRC risk, whereas fruit consumption (100 g/week) had a small inverse association and red meat consumption (100 g/week) a small direct association with CRC risk. Regardless, the substitutions with the plant-based foods appeared to strengthen the associations observed between red or processed meat consumption and CRC risk.
We observed a reduction in CRC risk when red meat or processed meat was partially substituted with vegetables or fruits. The beneficial effects of vegetables and fruits on CRC risk may arise from their high content of dietary fiber and polyphenols [
40]. Indeed, fibre has been consistently associated with lower CRC risk; its protective effects seem to be linked to its ability to increase stool volume and decrease transit time, as well as to its fermentation in the gut into short-chain fatty acids with anticarcinogenic properties [
41,
42]. The protective effects of polyphenols have been linked to their anti-inflammatory, antioxidant and pro-apoptotic features [
43]. Nevertheless, when examined individually, we did not detect any association between vegetable consumption and CRC risk. This diverges from the WCRF/AICR meta-analysis, in which a small inverse association was observed for the consumption of 100 g/d of vegetables in 11 studies [
13]. The association was, however, driven by one study, while most studies in the meta-analysis reported null associations. When fruit consumption was examined individually, we detected a small inverse association with CRC risk. In the WCRF/AICR meta-analysis, no association was observed in 13 studies, whereas another meta-analysis of 19 prospective studies reported a 3% reduction in CRC risk per 100 g/d increase in fruit consumption [
40]. As uncertainty remains in the evidence regarding both vegetables and fruits, more research is needed on the substitutions as well as their individual associations with CRC risk.
Contrary to our expectations, neither whole grain intake nor the partial substitution of red meat or processed meat with whole grains was associated with CRC risk. This is discordant with the consistent evidence in the literature of an inverse association between whole grain intake and CRC risk. The non-significant results in our study seemed to be linked to ATBC because after excluding it from the cohorts, we observed a statistically significant 7% decrease in CRC risk when red meat was substituted with whole grains. We hypothesized that this discrepancy could be attributed to the high whole grain intake in ATBC (700 g/week [100 g/d]). Therefore, we stratified the analysis by the median whole grain intake in the total population (587 g/week [84 g/d]). Following this, the substitutions of red or processed meat with whole grains were not statistically significantly associated with CRC risk among participants with ≥ median whole grain intake, whereas, among participants with < median whole grain intake, the substitutions were associated with up to 8% reduction in CRC risk. This risk reduction is the largest observed in our study for either red meat or processed meat. Moreover, as average whole grain intake levels of adults fall below 84 g/d in Finland (60 g/d) [
32] and in many other Western countries, such as Denmark (69 g/d) [
44], the UK (median 20 g/d) [
45], Italy (4 g/d) [
46], Australia (21 g/d) [
47] and the US (16 g/d) [
48], this result suggests that most adults in these countries would benefit from the substitution with whole grains. The non-significant association among those with higher than median whole grain intakes could arise from a plateau effect in health benefits after achieving a certain whole grain intake level. Nevertheless, evidence from meta-analyses does not currently support a non-linear association between whole grain intake and CRC [
15,
49]. Thus, more research is needed to better understand this phenomenon.
We did not model substitutions of red meat or processed meat with legumes because, in our study population, legume consumption of 100 g/week seemed to have a direct association with CRC risk. This finding was unexpected as in a recent meta-analysis of 29 case-control and cohort studies, a 100 g/d increase in legume consumption was associated with a 21% lower CRC risk [
50]. The direct association in our study is likely related to low legume consumption in the cohorts (28 − 70 g/week). The association could also be linked to other dietary components that legumes have traditionally been consumed with; for example, pea soup, which traditionally includes pork, is among the most frequently consumed legume-based dishes in Finland. Overall, the observed association should be interpreted cautiously.
We could have detected more substantial risk reductions by modelling daily rather than weekly substitutions. Nevertheless, as we aimed to investigate substitutions that would be easy to implement and maintain in real life, substituting all or most daily red or processed meat consumption would not have met these criteria. As regards real-life implications, within our study population, the modelled substitutions correspond to approximately one and a half days’ portion of red meat (100 g) and one day’s portion of processed meat (50 g) in a week. On a food level, 100 g of red meat approximately equals one small beef steak (cooked) and 50 g of processed meat half a sausage or 3 − 4 cold cuts. Regarding the plant-based substitutes, a 50 − 100 g portion corresponds, for whole grains, to 3 − 6 slices of whole grain bread or 1 − 2 big portions of cooked whole grain pasta; for vegetables 0.5 − 1 small portion of oven-roasted vegetables; and for fruits 0.5 − 1 small apple or (peeled) banana. As these examples demonstrate, the modelled substitutions were very moderate and would be achievable to most people. Moreover, even if the substitutions were doubled, the dietary changes would remain feasible for most.
Although the observed risk reductions were small, we consider the results encouraging; even small population-level changes towards more plant-based diets could reduce the CRC burden in the population. These findings support the implementation of public health strategies to promote more plant-based diets as part of CRC primary prevention. Moreover, on an individual level, the knowledge that already small changes towards more plant-based diets can benefit health might encourage a gradual transition to healthier and more sustainable diets.
The main strength of this study is the large, pooled study population from five Finnish cohorts with long median follow-up and comprehensive information on participants’ diet, lifestyle and health. Another key strength is the use of comprehensive and reliable cancer data from a nationwide cancer registry, which resulted in nearly complete case ascertainment in each cohort. Furthermore, we assessed dietary intake in each cohort with a validated FFQ, which is a widely accepted and commonly used dietary assessment method in epidemiological research.
This study also has limitations. Because the FFQ is based on self-reporting, it may expose the data to reporting biases (e.g., under- or overreporting) and misclassification. To diminish these effects, we adjusted the analyses for energy intake. Another limitation is the use of a single baseline measurement, for which we could not consider potential changes in food consumption over the follow-up. Regarding CRC, we did not analyse the subtypes (proximal and distal colon cancer, rectal cancer) separately owing to the low number of, especially, distal colon cancers. This is a limitation, as the subtypes may have different risk factors. Even though we adjusted the analyses for several key dietary and lifestyle factors, we cannot rule out residual confounding from other unmeasured factors (e.g., genetic factors). In the substitution analyses, we did not model the substitutions in an isocaloric manner but according to corresponding consumption quantities. Therefore, despite the adjustment for energy intake, the substitutions have likely resulted in residual differences in energy intake, which would be reflected in the consumption of other foods in the diet. Nevertheless, as the modelled substitutions were very moderate and on a weekly level, we presumed that the variation in energy intake would remain on a level that would not considerably change the participants’ nutritional profiles; even if the residual energy would be consumed as other foods considered unhealthy, such as sodas or pastry products, increase in their consumption would remain small. Finally, because of the more selected study population in ATBC (male smokers), the results may not be fully generalizable to the general adult population. For example, residual confounding by smoking likely remains. We were not able to examine the effect of smoking on our results by stratifying the substitution analyses by smoking status due to the low number of CRC cases in the remaining cohorts. Nonetheless, the adjustment for smoking in the remaining cohorts did not appear to have a notable effect on the results, and, apart from the substitutions with whole grains, the differences in the results between ATBC and the remaining cohorts were small. Moreover, we observed no heterogeneity between the cohorts. The results also appeared similar for women and men.
To conclude, our results suggested that even small, easily implemented partial substitutions of especially red meat, but also processed meat, with whole grains, vegetables, fruits or a combination of these could lower CRC risk in Finnish adults. These findings support the necessity of dietary shifts towards more plant-based diets for health and environmental reasons. More evidence is, however, required in real-life settings and different populations to better understand the implications of these substitutions on CRC risk. Furthermore, public health strategies to promote and support these dietary changes as a part of CRC primary prevention require more attention.
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